Abstract

OBJECTIVE:

UDP-glucuronosyltransferase (UGT) 2B7 was recently identified as the main enzyme mediating efavirenz N-glucuronidation. In this study, we determined whether selected UGT2B7 polymorphisms could be used to enhance the prediction of efavirenz plasma concentrations from CYP2B6 and CYP2A6 genotypes.

CONCLUSION:

Our findings demonstrate independent effects of CYP2A6 and UGT2B7 genetic variation on efavirenz disposition beyond that of the CYP2B6 polymorphisms. The development and testing of a pharmacogenetic algorithm for estimating the appropriate dose of efavirenz should incorporate genotypic data from both the oxidative and glucuronidation pathways.

Scatter plot showing the relationship between pharmacogenetic-predicted efavirenz mid-dose plasma concentrations (y-axis) and observed concentration (x-axis) in 94 HIV-infected patients. Log10 efavirenz mid-dose plasma concentrations predictions for each subject were made based on their genotype carrier status (CYP2B6 c.516TT, CYP2A6*9 or *17 and/or UGT2B7*1a as indicated by arrows) using the pharmacogenetic algorithm derived by multiple linear regression analysis (model and associated goodness of fit statistics are shown at the top of graph). Log10 efavirenz concentration units are back-transformed into linear units for presentation in the plot.